The Human Cell Atlas...The Human Cell Atlas Project Large • Adult human: ~2X10 13 cells (excluding...
Transcript of The Human Cell Atlas...The Human Cell Atlas Project Large • Adult human: ~2X10 13 cells (excluding...
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The Human Cell Atlas
Aviv Regev Department of Biology, MIT
Broad Institute Howard Hughes Medical Institute
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Cells are our core constituents
Cells are classified by characteristic molecules, structures, and functions
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Cells: a key intermediate from genotype to phenotype
Genotype Cell Phenotype
Knowing our cells is essential for functional dissection of genetic variants
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What is a cell atlas? 1. TYPE
2. STATE
3. LOCATION
5. LINEAGE
4. TRANSITIONS
Current knowledge partial, decades and centuries old
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Single cell genomics makes this possible
Core technology Computation Sample prep
May 2012: 18 cells July 2014: ~100,000 cells
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Emerging capabilities bring scale and resolution
Location Registry to 2D, 3D
Measurement DNA, RNA,
epigenome, protein
Scale 5,000 cells/sec; ¢2.8/cell prep
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Asian-American 24 yr old
768 blood DCs
pDC CD141-CD1c- CD1c+ CD141+
pDC
myeloid
Unique
New population: 1.9-3.2% of DCs; 0.04-0.064% of PBMCs Validated in 10/10 independent individuals Placed in lineage: a blood progenitor?
Already rapidly leading to new insights
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Already rapidly leading to new insights TYPE
STATE
LOCATION
LINEAGE
TRANSITIONS
Retina neurons
New human immune blood progenitor
‘Early responder’ immune cells
Fish embryo
Pathogenic T cells in MS model
Muscle cell differentiation CSC spectrum
in glioma
GSC BMP4
scRNA-Seq
In situ
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The sequencer: a microscope for the 21st century
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The Human Cell Atlas Project
What? A census of all cells • Types • States • Transitions • Location
Why? A reference map for function • Foundational, fundamental
knowledge
• Function of genetic variants
• Heterogeneity in disease
• Eventually characterize in individual patients
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The Human Cell Atlas Project
How? A unified project • Pilot project in complementary
systems (e.g., blood, gut, liver)
• Consortium with expert communities
• Standard, controlled process
• Shared analytical tools
• Drive costs to ~$0.15/cell*
Why? Standardized and impactful • Managed: Only standard
process ensures we are not deceived by noise
• Scale: Drive cost down
• Technology advancing: Novel sample prep, cell isolation, analytical tools
• Resources for entire community
• Commensurate with clinic
* with drops, 105 reads/cell, @ $0.4-0.6/cell with HiSeq X10 yields
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The Human Cell Atlas Project
Large • Adult human: ~2X1013 cells
(excluding red blood cells) • 300 ‘major’ cell types
• ….but, ~100 sub-sub-types just
of retinal neurons
… but finite
150M neurons in retina, ~40K required for survey
Retinal bipolar cell (BC): 12 sub types, rarest @5% Retinal amacrine cell (AC): 50 subtypes, rarest @1% Retinal Ganglial cell (RGC): 30 subtypes, rarest @1%
Photoreceptors (3) Horizontal cells (1) Bipolar cells (12) Amacrine cells (50) RGCs (30)
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